Evaluación in vitro de los agentes neurotóxicos liberados por las células de la microglía, infectadas con el virus dengue neuroadaptado (D4MB-6)

dc.contributor.advisorVelandia-Romero, Myriam Lucía
dc.contributor.advisorCastellanos, Jaime
dc.contributor.authorBeltrán Zúñiga, Edgar Orlando
dc.contributor.orcidCastellanos, Jaime [0000-0003-1596-8383]
dc.contributor.orcidVelandia-Romero, Myriam Lucía [0000-0002-3340-7304]
dc.date.accessioned2021-02-22T21:21:43Z
dc.date.available2021-02-22T21:21:43Z
dc.date.issued2021
dc.description.abstractLa infección causada por el virus del dengue (DENV) se ha relacionado con el desarrollo de alteraciones neurológicas y comportamentales en humanos. Dicha asociacione se ha confirmado por el desarrollo de signos claros de alteración neurológica durante y después de la infección y por la presencia de proteínas y/o RNA viral en líquido cefaloraquídeo o en muestras de tejido nervioso obtenidas post morten. Esto sugiere que el virus puede invadir el Sistema Nervioso Central (SNC). Por la dificultad de reproducir los signos y síntomas del dengue en animales, nuestro grupo desarrolló un modelo in vivo de neuroinfección en el cual ratones neonatos se inocularon a nivel periférico con una cepa de virus adaptada a tejido nervioso (D4MB-6). Como resultado, se observó que la variante viral logró invadir el SNC e infectó algunas poblaciones celulares como neuronas, oligodendrocitos y células de la microglía. Estas últimas presentaron evidentes cambios morfológicos que sugerían activación. Adicionalmente se observó que en el tejido nervioso de animales infectados la infección indujo una exacerbada respuesta inmune y la excitotoxicidad por glutamato, espectos que en conjunto causaron la muerte neuronal y el daño en la arquitectura tisular. Sin embargo, la población celular del tejido nervioso que secreta estas moléculas no ha sido identificada aún. Experimentalmente se ha demostrado que en diferentes patologías -incluso virales- la principal fuente de citoquinas pro-inflamatorias, glutamato y otros agentes provienen de las células de la microglía infectadas y/o activadas. Todos los agentes producidos y liberados por estas células, pueden de manera conjunta o independiente ocasionar el daño y la muerte neuronal. Por lo tanto, en este trabajo se evaluó en un cultivo primario de células de la microglía de ratón lactante, su susceptibilidad a la infección con la variante adaptada -D4MB-6- o no a tejido nervioso y algunos aspectos relacionados con su activación. Como resultado se observó que las células microgliales presentaron una alta susceptibilidad a la infección y en los tiempos post-infección evaluados presentaron altas tasas de proliferación y supervivencia. Adicionalmente se observó que las células presentaron cambios morfológicos y produjeron algunas moléculas pro-inflamatorias y glutamato, que indujeron a las células a sostener en los tiempos evaluados un estado de activación que fue modulado y regulado por los fármacos VPA o MK-801. En conjunto estos resultados permitieron describir que la infección por DENV indujo la activación y producción de agentes pro-inflamatorios y glutamato por parte de las células de la microglía, por lo tanto, sugerimos que estas células son centrales en el desarrollo de la nueuroinfección y neuropatogenia causada por el DENV.spa
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias Básicas Biomédicasspa
dc.format.mimetypeapplication/pdf
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/5409
dc.publisher.facultyFacultad de Medicinaspa
dc.publisher.grantorUniversidad El Bosquespa
dc.publisher.programMaestría en Ciencias Básicas Biomédicasspa
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dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.creativecommons2016
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCélulas de la microglíaspa
dc.subjectNeuropatogeniaspa
dc.subjectDENVspa
dc.subjectVirus neuroadapatadospa
dc.subjectActivación celularspa
dc.subject.decsNeurotoxinasspa
dc.subject.decsTécnicas in vitrospa
dc.subject.decsVirus del denguespa
dc.subject.nlmW 50
dc.titleEvaluación in vitro de los agentes neurotóxicos liberados por las células de la microglía, infectadas con el virus dengue neuroadaptado (D4MB-6)spa
dc.title.translatedIn vitro assessment of the neurotoxic agents produced by infected microglial cells by a neuroadapted strain of Dengue Virus-D4MB-6spa
dc.type.coarhttps://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttps://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersion
dc.type.localTesis/Trabajo de grado - Monografía - Maestríaspa

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